Assessment of the systemic distribution of a bioconjugated anti-Her2 magnetic nanoparticle in a breast cancer model by means of magnetic resonance imaging

  • L. F. E. Huerta-Núñez
  • G. Cleva Villanueva-Lopez
  • A. Morales-Guadarrama
  • S. Soto
  • J. López
  • J. G. Silva
  • N. Perez-Vielma
  • E. Sacristán
  • Marco E. Gudiño-Zayas
  • C. A. González
Research Paper


The aim of this study was to determine the systemic distribution of magnetic nanoparticles of 100 nm diameter (MNPs) coupled to a specific monoclonal antibody anti-Her2 in an experimental breast cancer (BC) model. The study was performed in two groups of Sprague–Dawley rats: control (n = 6) and BC chemically induced (n = 3). Bioconjugated “anti-Her2-MNPs” were intravenously administered, and magnetic resonance imaging (MRI) monitored its systemic distribution at seven times after administration. Non-heme iron presence associated with the location of the bioconjugated anti-Her2-MNPs in splenic, hepatic, cardiac and tumor tissues was detected by Perl’s Prussian blue (PPB) stain. Optical density measurements were used to semiquantitatively determine the iron presence in tissues on the basis of a grayscale values integration of T1 and T2 MRI sequence images. The results indicated a delayed systemic distribution of MNPs in cancer compared to healthy conditions with a maximum concentration of MNPs in cancer tissue at 24 h post-infusion.


Breast cancer Magnetic nanoparticles Anti-Her2 Systemic distribution Magnetic resonance imaging Nanomedicine 



Magnetic nanoparticles


Breast cancer


Human epidermal growth factor receptor 2


Monoclonal antibody


Magnetic resonance imaging


Perl’s Prussian blue


International Agency for Research on Cancer


Growth factor receptor-bound protein 2




Radiofrequency ablation


Tumor-associated macrophages

MMTV–PyMT mice

Mice with spontaneous multifocal mammary tumors and high incidence of pulmonary metastasis




Iron oxide nanoparticles


Transmission electron microscopy

Fe3O4 MNPs

Magnetic iron nanoparticles


Ultrasmall supermagnetic iron oxide


Small supermagnetic iron oxide


N-methyl nitrosourea




Fluorescein isothiocyanate


Ethanesulfonic acid


Phosphate-buffered saline


Gradient-echo multislice sequence


Fast spin-echo multislice sequence



This work was developed in the Laboratory of Physiology of the “Escuela Militar de Graduados de Sanidad-Universidad del Ejército y Fuerza Aérea” (EMGS-UDEFA), in the Oxidative Stress Laboratory “Escuela Superior de Medicina del Instituto Politécnico Nacional” as well as in the “Centro de Investigación en Instrumentación e Imagenología Médica, Universidad Autónoma Metropolitana-Iztapalapa” México and was supported by “CONACYT CB-2012” under Grant No. 180536.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.


  1. Abramson V, Arteaga CL (2011) New strategies in HER2-overexpressing breast cancer: many combinations of targeted drugs available. Clin Cancer Res 17:952–958CrossRefGoogle Scholar
  2. Brannon-Peppas L, Blanchette JO (2004) Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliv Rev 56:1649–1659CrossRefGoogle Scholar
  3. CHEMICELL at http// 1st Nov 2015
  4. Daldrup-Link HE, Golovko D, Ruffell B, Denardo CR, Ansari C et al (2011) MRI of tumor-associated macrophages with clinically applicable iron oxide nanoparticles. Clin Cancer Res 17(17):5695–5704CrossRefGoogle Scholar
  5. DeNardo SJ, DeNardo G, Miers LA, Natarajan A, Foreman AR, Gruettner C et al (2005) Development of tumor targeting bioprobes (111In-chimeric L6 monoclonal antibody nanoparticles) for alternating magnetic field cancer therapy. Clin Cancer Res 11(19 Pt 2):7087s–7092sCrossRefGoogle Scholar
  6. Duncan R, Gaspar R (2011) Nanomedicine(s) under the microscope. Mol Pharm 8(6):2101–2141CrossRefGoogle Scholar
  7. Giustini JA, Ivkov R, Hoopes JP (2011) Magnetic nanoparticle biodistribution following intratumoral administration. Nanotechnology 22(34):345101CrossRefGoogle Scholar
  8. Giustini JA, Petryk AA, Hoopes JP (2012) Ionizing radiation increases systemic nanoparticle tumor accumulation. Nanomedicine 8(6):818–821Google Scholar
  9. Huang HS, Hainfeld JF (2013) Intravenous magnetic nanoparticle cancer hyperthermia. Int J Nanomed 8:2521–2532Google Scholar
  10. Ilinskaya AN, Dobrovolskaia MA (2013) Nanoparticles and the blood coagulation system. Nanomedicine 8(5):773–784CrossRefGoogle Scholar
  11. Khosravi Shahi P, Pérez Manga G (2006) La relevancia clínica de la sobreexpresión de HER-2 en el cáncer de mama. An Med Interna (Madrid) 23(3):103–104CrossRefGoogle Scholar
  12. Kirpotin DB, Drummond DC, Shao Y, Shalaby R, Hong K, Nielsen UB et al (2006) Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models. Cancer Res 66(13):6732–6740CrossRefGoogle Scholar
  13. Kreb DL, Looij BG, Ernst MF, Rutten MJCM, Jager GJ, der Linden Van et al (2013) Ultrasound-guided radiofrequency ablation of early breast cancer in resection specimen. Lesson for further research. Breast 22(4):543–547CrossRefGoogle Scholar
  14. Laurent S, Mahmoudi M (2011) Superparamagnetic iron oxide nanoparticles: promises for diagnosis and treatment of cancer. Int J Mol Epidemiol Genet 2(4):367–390Google Scholar
  15. Manenti G, Bolacchi F, Perretta T, Cossu E, Pistolese CA, Buonomo OC et al (2009) Small breast cancers: in vivo percutaneous US-guided radiofrequency ablation with dedicated cool-tip radiofrequency system. Radiology 251(2):339–346CrossRefGoogle Scholar
  16. Manenti G, Scarano AL, Pistolese CA, Perretta T, Bonanno E, Orlandi A et al (2013) Subclinical breast cancer: minimally invasive approaches. our experience with percutaneous radiofrequency ablation vs. cryotherapy. Breast Care 8(5):356–360CrossRefGoogle Scholar
  17. Silva JG, Sánchez V, Polo SM, González CA (2013a) Expression of c-erbB-2 in breast cancer cell lines as experimental receptor of magnetic nanoparticles. In: Conference proceedings IEEE engineering in medicine and biology society, July, Osaka, pp 4498–4501Google Scholar
  18. Silva JG, Maldonado J, Tapia JS, Herrera NE, Polo SM, Martínez SG, González CA (2013b) Selective targeting of breast cancer cells MCF-7 by ferromagnetic nanoparticles. In: Proceedings of the V latin American congress on biomedical engineering CLAIB 2011, IFMBE proceedings, vol 33, pp 983–986Google Scholar
  19. Silva JG, López J, Sánchez V, Lozano L, Gonzalez C (2015) Breast cancer tissue marked selectively by magnetic nanoparticles in an experimental animal model. J Nanoasci Nanotechnol 15:1–6 (ISSN: 1533-4880) CrossRefGoogle Scholar
  20. Silva-Escobedo JG, Sánchez-Monroy V, Rojas-Lopez M, Lopez-Cruz J, Gonzalez CA (2014) C-erbB-2 as a possible target for the use of magnetic nanoparticles in breast cancer cells. IEEE Trans Nanobiosci 13(3):300–307CrossRefGoogle Scholar
  21. Slamon DJ, Clark GM, Wong SG, Levine WJ, Ullrich A, Human MWL (1987) Breast cancer. Correlation of relapse and survival with amplification of the HER-2/neuoncogene. Science 235:177–182CrossRefGoogle Scholar
  22. Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE et al (1989) Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244:707–712CrossRefGoogle Scholar
  23. Storm G, Belliot SO, Daemen T, Lasic DD (1995) Surface modification of nanoparticles to oppose uptake by the mononuclear phagocyte system. Adv Drug Deliv Rev 17:31–48CrossRefGoogle Scholar
  24. Thompson JH, Adlakha H (1991) Dose-responsive induction of mammary gland carcinomas by the intraperitoneal injection of 1-methyl-l-nitrosourea. Cancer Res 51:3411–3415Google Scholar
  25. Tsuchiya K, Nitta N, Sonoda A, Nitta-Seko A, Ohta S, Otani H et al (2011) Histological study of the biodynamics of iron oxide nanoparticles with different diameters. Int J Nanomed 6:1587–1594CrossRefGoogle Scholar
  26. Wang J, Chen Y, Chen B, Ding J, Xia G, Gao C et al (2010) Pharmacokinetic parameters and tissue distribution of magnetic Fe3O4 nanoparticles in mice. Int J Nanomed 5:861–866Google Scholar
  27. Weissleder R, Stark DD, Engelstad BL, Bacon BA, Compton CC, White DL et al (1989) Superparamagnetic iron oxide: pharmacokinetics and toxicity. Am J Roentgenol 152:167–173CrossRefGoogle Scholar
  28. Yoshinaga Y, Enomoto Y, Fujimitsu R, Shimakura M, Nabeshima K, Iwasaki A (2013) Image and pathological changes after radiofrequency ablation of invasive breast cancer: a pilot study of nonsurgical therapy of early breast cancer. World J Surg 37(2):356–363CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • L. F. E. Huerta-Núñez
    • 1
  • G. Cleva Villanueva-Lopez
    • 2
  • A. Morales-Guadarrama
    • 3
  • S. Soto
    • 1
  • J. López
    • 1
  • J. G. Silva
    • 1
  • N. Perez-Vielma
    • 4
  • E. Sacristán
    • 3
  • Marco E. Gudiño-Zayas
    • 5
  • C. A. González
    • 1
    • 2
  1. 1.Universidad del Ejercito y FAM/EMGS-Laboratorio Multidisciplinario de InvestigaciónMexico CityMexico
  2. 2.Instituto Politécnico Nacional-Escuela Superior de Medicina-Sección Investigación y PosgradoMexico CityMexico
  3. 3.Centro Nacional de Investigacion en Imagenologia e Instrumentacion Medica-Universidad AutónomaMexico CityMexico
  4. 4.Instituto Politécnico Nacional - Centro Interdisciplinario de Ciencias de la Salud Unidad Santo Tomás (CICS-UST)Mexico CityMexico
  5. 5.Departamento de Medicina Experimental, Facultad de MedicinaUNAMMexico CityMexico

Personalised recommendations